Isopropanol → 2-(4-((3-(Piperazin-1-YL)pyrazin-2-YL)oxy)piperidin-1-YL)quinoline

HRID 454923Notes

Reaction equation

Cl[C:2]1[C:3]([O:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:24]=[CH:23][C:22]4[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=4)[N:16]=3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[CH:6][N:7]=1.[NH:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1.C([O-])([O-])=O.[K+].[K+].CC(O)C>O>[N:25]1([C:2]2[C:3]([O:8][CH:9]3[CH2:14][CH2:13][N:12]([C:15]4[CH:24]=[CH:23][C:22]5[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=5)[N:16]=4)[CH2:11][CH2:10]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1

Participants

Conditions

Temperature: 160 °C

Procedure

To a mixture of 2-(4-((3-chloropyrazin-2-yl)oxy)piperidin-1-yl)quinoline (see PREPARATION P2.1; 0.34 g, 1.0 mmol) and piperazine (0.83 g, 1.0 mmol) and K2CO3 (0.27 g, 2.0 mmol) was added i-PrOH (2 mL) and water (0.5 ml). The solution was heated to 160° C. under microwave for 5 hours. Then the mixture was concentrated and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether) to give the title product (0.11 g, 0.30 mmol, 30% yield) as white solid. ESI-MS (M+1): 391 calc. for C22H26N6O 390.

Workup

concentrationThen the mixture was concentrated
extractionextracted with EtOAc (2×20 mL)
washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
customThe filtrate was evaporated in vacuo
customthe residue was purified by flash column chromatography on silica gel (20% to 60% EtOAc in petroleum ether)

Sources & evidence

ORD record: ord-7d715bf7f1244777999c27d3c863faa7
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08497265B2

Reaction notes

Loading…